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Introduction: Immediate-release memantine (10 mg, twice daily) is approved in the USA for moderate-to-severe Alzheimer's disease (AD). This study evaluated the efficacy, safety, and tolerability of a higher-dose, once-daily, extended-release formulation in patients with moderate-to-severe AD concurrently taking cholinesterase inhibitors., Methods: In this 24-week, double-blind, multinational study (NCT00322153), outpatients with AD (Mini-Mental State Examination scores of 3-14) were randomized to receive once-daily, 28-mg, extended-release memantine or placebo. Co-primary efficacy parameters were the baseline-to-endpoint score change on the Severe Impairment Battery (SIB) and the endpoint score on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). The secondary efficacy parameter was the baseline-to-endpoint score change on the 19-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19); additional parameters included the baseline-to-endpoint score changes on the Neuropsychiatric Inventory (NPI) and verbal fluency test. Data were analyzed using a two-way analysis of covariance model, except for CIBIC-Plus (Cochran-Mantel-Haenszel test). Safety and tolerability were assessed through adverse events and physical and laboratory examinations., Results: A total of 677 patients were randomized to receive extended-release memantine (n = 342) or placebo (n = 335); completion rates were 79.8 and 81.2 %, respectively. At endpoint (week 24, last observation carried forward), memantine-treated patients significantly outperformed placebo-treated patients on the SIB (least squares mean difference [95 % CI] 2.6 [1.0, 4.2]; p = 0.001), CIBIC-Plus (p = 0.008), NPI (p = 0.005), and verbal fluency test (p = 0.004); the effect did not achieve significance on ADCS-ADL19 (p = 0.177). Adverse events with a frequency of ≥5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9 %)., Conclusion: Extended-release memantine was efficacious, safe, and well tolerated in this population.

Background: Caring for a person with dementia is associated with well-documented increases in burden and distress and decreases in mental health and wellbeing. Studies assessing burden in caregivers of patients with dementia and its determinants are scarce in Latin America., Objective: The main objective of this study was to assess the extent and the determinants of burden in informal primary caregivers of patients with dementia in Chile., Methods: A descriptive study was conducted using clinically validated scales to assess dementia characteristics and to measure caregiver variables. Family socio-demographic characteristics and functional status, patient functional dependency and behavioral disturbances, and caregiver psychiatric morbidity were analyzed as independent variables to determine caregiver burden., Results: Two hundred and ninety-two informal caregivers were included. There were more female (80%) than male caregivers, consisting mainly of daughters and spouses of the patients. Severe burden was reported in 63% of the caregivers, and 47% exhibited psychiatric morbidity. Burden was associated with caregiver psychiatric distress, family dysfunction, severity of neuropsychiatric symptoms and functional disability, but neither patient age, gender, nor socioeconomic status impacted burden., Conclusion: Our results underscore the importance of assessing the consequences of dementia in both caregivers and patients in order to evaluate the real biopsychosocial impact of dementia, as well as the importance of planning appropriate and effective public health interventions in Latin American countries. In addition, interventions targeting caregiver psychological distress, caregiver familial dysfunction, patient neuropsychiatric disorders, and patient functional disability could potentially diminish caregiver burden.

We here described a 39-year-old woman with a severe chronic mood disorder, refractory to antidepressive therapy who showed a significant improvement after a self-prescription of high doses of liothyronine (T(3)). A modified Refetoff protocol was carried out to study the role of thyroid hormones on her clinical and biochemical responses. Depression severity was assessed by the HAM-D and MADRS Depression Rating Scales. Sequencing of Thyroid Receptors (TR) alpha1 and beta1 genes was done. At the final stage of the study, plasma T3 and free T3 were >800 ng/dl (80-180) and 1409 pg/dl (230-420), respectively. No changes in the cardiovascular parameters, alkaline phosphatase isoenzymes, creatinine kinase, or ferritin were observed. However, an improvement in mood was detected by specific scores (HAM-D 24 to 8; MADRS 40 to 11). No mutations in DNA- and hormone-binding-domains of TRbeta1 and TRalpha1 genes were found in proband, suggesting that the defect could be due to an unknown mutation in either the TR gene or a post receptor abnormality. These results support the existence of a peripheral RTH manifestation as a refractory chronic depression reverted by high doses of T(3). Screening for RTH in refractory chronic depression may provide an alternative treatment for this psychiatric condition.

Background: Thyroid dysfunction is frecuent in psychiatric outpatients and in the general Chilean population but there is no information about the prevalence of thyroid diseases in Chilean psychiatric inpatients., Aim: To retrospectively assess the frequency of thyroidal diseases in psychiatric inpatients., Material and Methods: Clinical charts and thyroid assessment of 241 psychiatric inpatients (147 women, mean age 33+/-16 years) attended in a University Psychiatric Clinic, were reviewed. Psychiatric diagnosis at discharge was made according to DSM IV criteria and endocrine diagnosis was made based on international criteria., Results: Forty nine patients (20.7%) had thyroid abnormalities. Forty four patients had hypothyroidism (18.3%) and five had hyperthyroidism (2.35%). No specific associations were found between gender or psychiatric diagnosis and endocrine abnormalities., Conclusions: In this sample, the prevalence of thyroid abnormalities was similar to other reports in psychiatric inpatiens and higher than in the general population in Chile.

For more than 40 years thyroid hormones and mood disorders have been associated. Some psychiatric symptoms are produced by thyroid illnesses and there is a frequent association of thyroid dysfunction with mood disorders. Therefore, routine thyroid function assessment in patients with mood disorders and the treatment of sub-clinical thyroid dysfunctions is recommended. The usefulness of adding thyroid hormones to antidepressive treatment in euthyroid patients to obtain a potentiation effect has been probed repeatedly. The most common strategy is potentiation with T3, but high doses of T4 have been also used in patients with resistant depression. Thyroid hormones exert their action in the central nervous system through a variety of mechanisms: modulation of gene expression of several groups of proteins, some of them with known physiopathological implications in mood disorders and the influence over serotonin and noradrenergic neurotransmission, known to be one of the modes of action of antidepressants. Finally, it is also important to stress the complex relationship between psychiatric drugs, deiodinases and thyroid hormones, that can potentially help to understand the mechanisms of action of these drugs.

Clinical studies have demonstrated that neuropsychiatric symptoms may be common and often the only symptoms of patients affected by hyperthyroidism. The correct diagnosis of hyperthyroidism is crucial for optimal treatment because the neuropsychiatric symptoms tend to parallel resolution as the biochemical parameters of hyperthyroidism are normalized. For these reasons, a routine evaluation in every patient consulting for emotional pathologies is recommended, independent of other manifestations of thyroid disease. The effect of high levels of thyroid hormones in the CNS has been related to changes in the presence of alpha- and beta-adrenergic postsynaptic receptors, or more recently to changes in the serotonin concentration. However, the available information is incomplete and many questions remain to be answered in order to explain how the thyroid hormone modifies the CNS response. Increased knowledge of the molecular targets (i.e., genes) of thyroid hormones in the brain may help to provide an answer to these questions.

Background: There is no information about the prevalence of thyroidal diseases in the general Chilean population., Aim: To assess the prevalence of thyroidal diseases in individuals attended in occupational health examinations., Subjects and Methods: Four hundred seventy two individuals were examined between 1998 and 1999. In all, serum levels of thyroid hormones, TSH and anti thyroidal antibodies (anti microsomal, anti thyroid peroxidase and anti thyroglobulin) were measured., Results: Forty four subjects were excluded from the study due to an incomplete medical record and 18 due to a personal history of thyroidal disease. Abnormal serum levels of thyroid hormones or TSH were detected in 28 subjects (6.8%). Four (1%) had hypothyroidism, 23 a subclinical hypothyroidism (5.6%) and one (0.2%) had hyperthyroidism. In 87 subjects (21.2%) at least one of the antibodies was positive. Positive anti thyroid antibodies were found in 14 of 28 subjects (50%) with abnormal thyroid hormone levels, compared with 73 of 382 subjects (19.1%) with normal thyroid hormone levels. Thyroid dysfunction was twice as frequent in women than in men., Conclusions: In this sample, a 6.8% prevalence of abnormal thyroid function tests was detected.

In two females aged 27 and 32 years old, an aggravation of their panic disorder coincided with the appearance of clinical signs of hyperthyroidism. The clinical diagnosis was confirmed with the finding of raised thyroid hormone levels and undetectable TSH levels. These two cases highlight the importance of routine thyroid function assessment in patients with panic disorder, mainly in those with partial response to medications or when symptoms aggravate, despite an adequate treatment.

Background: Thyroid dysfunction is frequent in psychiatric outpatients and the correction of their endocrine abnormalities seems to improve the response to psychopharmacologic treatment., Aim: To retrospectively explore the frequency of thyroid abnormalities in psychiatric outpatients., Material and Methods: Clinical charts and thyroid assessment of 102 psychiatric patients aged 40.8 +/- 15 years old (28 male) seen between April 1995 and September 1996 were reviewed. Endocrine diagnosis was made according to international criteria and psychiatric diagnosis was made by a single psychiatrist following DSM IV criteria., Results: Forty patients (39.2%) had thyroid abnormalities. Thirteen (12.7%) had a diagnosis of thyroid problems and were in treatment before they came to the psychiatric clinic. Sixteen patients had hypothyroidism (40%), seven had subclinical hypothyroidism (17.5%), 12 were euthyroid but had goiter or positive thyroid antibodies (30%) and 5 individuals had hyperthyroidism (12.5%). The most frequent thyroid abnormality was the presence of positive thyroid antibodies in 16 cases (15.7%). No specific association was found between psychiatric and endocrine diagnoses., Conclusions: The design of this study prevents to draw conclusions about prevalence of thyroid alterations in psychiatric patients. Nevertheless results support the need for routine thyroid assessment in this specific population.

Background: There is a relationship between stressful situations and the susceptibility towards certain diseases, probably mediated by immune system modifications., Aim: To study T lymphocyte proliferation in medical students during periods of differing academic stress., Subjects and Methods: Blood samples were obtained from 42 medical students during a period of moderate academic stress, immediately before a final examination and after their summer vacations. T lymphocyte proliferation in response to 5, 10 and 20 mg/ml phytohemagglutinin was measured by the incorporation of 3H-thymidine, and plasma cortisol was measured by RIA., Results: T lymphocyte stimulation index in response to all phytohemagglutinin concentrations was significatively lower in the period before examination than in the other two periods. There were no differences in the index between the period of moderate stress and after summer vacations. Plasma cortisol levels were 15.6 +/- 4.3, 18.6 +/- 5.8 and 16.7 +/- 5.1 mg/dl during the periods of moderate stress, before the examination and after vacations, respectively (p < 0.05 for the difference between examination and the other two periods)., Conclusions: There is a decrease in lymphocyte proliferation and an increase in cortisol levels during a period of acute academic stress in medical students, suggesting that, the exposure of the healthy subjects to common stressful stimuli, may affect their immunocompetance.

In the psychiatric literature, panic attacks have been considered as part of the clinical manifestations of anxiety neurosis, agoraphobia, functional cardiovascular disturbances, and the phobic depersonalization syndrome. Even though recurrent spontaneous panic attacks are described in these entities, the importance ascribed to them has been minor one. Therefore, panic attacks are poorly understood from a psycho-physio pathological point of view. In the past years, new trends in the nosology of psychiatric disorders have grouped the recurrent spontaneous panic attacks under the heading "panic disorder and agoraphobia with panic attacks." In this view, we present the results of the controlled pharmacological trials on patients complaining of panic attacks. Some relationships between panic attacks, panic disorder, and agoraphobia are discussed.

Clomipramine (25-150 mg/day) was given in a 2-month open clinical trial to patients with DSM-III defined panic disorder (N = 8) or agoraphobia with panic attacks (N = 12); 6 of these patients were found to have MVP. Substantial improvement was seen in all of the patients with MVP and 11 of 14 without MVP. Response was not affected by age, sex, or agoraphobic vs panic disorder diagnosis. Thus, clomipramine appears effective in the treatment of spontaneous panic attacks with or without mitral valve prolapse.

Seventeen outpatients with panic anxiety and agoraphobia were treated with a low, flexible dose of clomipramine in an 8-week open trial. Panic attacks ceased completely in 13 patients and markedly decreased in the other four without additional therapeutic measures. Avoidance behavior disappeared in five of the seven agoraphobic patients. Overall mean dosage was 45 mg/day, with eight patients receiving clomipramine 25 mg or less. Higher doses were needed when agoraphobia was present. These results are discussed in conjunction with previous findings and lend support to serotonergic involvement in panic anxiety. Further double-blind studies are needed to confirm these results.

Recent advances in psychiatric nosology have provided a clearer clinical description of panic disorder and agoraphobia with panic attacks. This clinical improvement has yet to result in a better understanding of the basic mechanisms involved in these conditions. The present study compares the effects of the cold pressor test on blood pressure changes and prolactin levels in patients with panic disorder and agoraphobia with panic attacks to its effects in normal controls. Because the effects of the cold pressor test were similar in patients and normal controls, it appears that alpha-adrenergic function is normal in the patient group. The results also suggest that prolactin hypersecretion does not occur in pathological anxiety states.

Patients complaining of recurrent spontaneous panic attacks (RSPA) are frequently seen in emergency rooms and psychiatric outpatient services. The symptomatology of RSPA suggests some underlying cardiac pathology. Recent publications in the psychiatric literature have reported a high incidence of mitral valve prolapse (MVP) in patients complaining of RSPA. In our study we report a 39% incidence of MVP in a psychiatric population with RSPA. The importance of this finding is yet to be determined.

Recurrent spontaneous panic attacks are psychophysiological symptoms present in panic disorder and agoraphobia with panic attacks. Effective pharmacological treatment for panic attacks is essential to any treatment plan for these conditions. The authors administered chlomipramine to 20 patients who had panic disorder or agoraphobia with panic attacks, and after 8 weeks of treatment 75% of the patients with each diagnosis were asymptomatic. These results support the claim that chlomipramine is highly effective in preventing recurrence of panic attacks.